Breakthrough infections after COVID-19 vaccines: Who is at risk?

While the rate of breakthrough infections is low among people who have been fully vaccinated against COVID-19, researchers found that older age and having anaemia were associated with an increased risk of such infections.

“Despite high efficacy and effectiveness [of COVID-19 vaccines], there are anecdotal reports of breakthrough infection among vaccine recipients,” the researchers stated.

To examine the rate and risk factors related to infections after receiving the recommended course of vaccination, researchers analysed data of 258,716 fully vaccinated persons based on health records from The Veterans Health Administration (VA). All participants had received two doses of mRNA-based vaccines between December 2020 and March 2021. [J Infect 2021;doi:10.1016/j.jinf.2021.05.021]

Based on PCR testing of nasopharyngeal swab sampled >7 days after the second vaccination dose, participants with confirmed SARS-CoV-2 infection were defined as cases (n=410, median age 73 years) whereas those who remained uninfected with ≥1 negative test for SARS-CoV-2 beyond 7 days after their second dose of vaccine were taken as controls (n=14,465, median age 72 years).

Overall, the breakthrough infection rate beyond 7 days after the second dose of vaccination was low, at 0.66 (95 percent confidence interval [CI], 0.60–0.72) per 1,000 person-days of follow-up.

Specifically, infection rates were higher among individuals with comorbidities than those with none (rate per 1,000 person-days, 0.68 to 0.69 in those with ≥1 comorbidity vs 0.44 in those with none). The comorbidities assessed included anaemia, coronary artery disease, diabetes, chronic kidney disease, COPD*, HIV, and cancer diagnosis.

Among the subgroup with comorbidities, having more number of comorbidities was not significantly associated with an increased risk of breakthrough infections per se — but having anaemia, in particular, was associated with a higher risk (hazard ratio [HR], 1.37, 95 percent CI, 1.09–1.73; p=0.01).

“The reason for the association of anaemia with infection after vaccination while no association was demonstrable other comorbidities is unclear,” said the researchers. “We did not assess the association of the degree of anaemia with the risk of infection. Whether this association is limited to more severe anaemia, which may worsen oxygenation, is not known.”

Another factor associated with SARS-CoV-2 breakthrough infections was older age. For every 10 years increment in age, the risk of infection increased by 11 percent (HR, 1.11, 95 percent CI, 1.01–1.23; p=0.04).

“Increasing age is a well-recognized risk factor for SARS-CoV-2 infection and is also associated with more severe disease and poorer clinical outcomes. Therefore, it is not surprising that it would also be associated with infection after vaccination,” the researchers explained.

“The rate of infection among persons who have been fully vaccinated is low but not insignificant. Increasing age and presence of anaemia increase the risk,” they summed up. “An awareness campaign, particularly targeted to those at risk is needed to mitigate the risk.”

As the data was based on the VA database, most veterans are male, which the authors recognized as a study limitation. They also did not assess the disease severity and outcomes in this study, which they said would be the topic of their future research. 

*COPD: Chronic obstructive pulmonary disease